不对称的整体合成的ent-(-) -roseophilin:分配绝对配置的绝对配置
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
研究人员合成了抗瘤抗生素roseophilin的非自然反体. 这种非自然形式的素,素,在细胞毒性测试中出乎意料地显示出比天然素的效果大2-10倍.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成化学 合成化学
背景情况:
- 罗斯菲林是一种天然存在的抗瘤抗生素.
- 天然素的绝对立体化学以前没有被分配.
- 合成非自然的反反体,--素,是为了帮助立体化学赋值,并探索结构-活性关系.
研究的目的:
- 为了实现一个不对称的整体合成的ent-(-) -roseophilin.
- 为了证实天然色素的绝对立体化学.
- 为了评估与天然产品相比,--素的细胞毒性活性.
主要方法:
- 反向电子需求在四氨酸和乙醇乙烯之间发生迪尔斯-阿尔德反应.
- 减少环收缩以形成醇.
- 格鲁布斯关于宏观循环形成的环闭转化论.
- 为了引入环坦的激进循环化.
- 凝结和去除保护的步骤.
主要成果:
- 成功的非对称的整体合成的ent-(-) -roseophilin ((22S,23S) -1).
- 与天然素的比较证实了反体关系,并将天然产品的立体化学赋予了22R,23R.
- 在细胞毒性试验中,ent-(-) - - 素的强度比天然 (+) - - 素高出2-10倍.
结论:
- 这项研究确定了一条合成途径,以获得ent-(-) -roseophilin.
- 自然素的绝对立体化学被分配为22R,23R.
- 非自然的反体显示出显著增强的抗瘤活性,表明潜在的治疗优势.
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